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Nuclear medicine is an important tool for use in molecular imaging of important biological processes. Methods for intravenous delivery of radiotracers remains a challenge, with tail vein injections demonstrated to be technically difficult and lacking in reproducibility. Other intravenous methods include jugular vein (JV) injection, which requires a more invasive and precise microsurgical technique. Although the retroorbital (RO) sinus drains directly into the JV, and RO injections are minimally invasive and simpler to perform, they remain underutilized, perhaps due to a lack of studies demonstrating their performance. This study provides a comprehensive comparison of dynamic tissue biodistribution of three categories of commonly utilized radiopharmaceuticals between JV and RO injection methods in prostate tumor-bearing mice using PET-CT imaging. Results show that JV and RO injections have equivalent dynamic tissue biodistributions across the three categories of radiopharmaceuticals used: (1) small molecule measuring tumor metabolism ( 18 F-flurodeoxyglucose [FDG]); (2) peptide-based probe measuring angiogenesis ( 64 Cu-NOTA-PEG 4 -cRGD 2 ); and (3) dextran-based nanocarrier ( 64 Cu-NOTA-D20). Although RO injections present with some limitations such as type of injectate and difficulty for measuring acute, dynamic pharmacokinetics, this study demonstrates that RO injections are a viable, minimally invasive or stressful, and efficient alternative intravenous delivery technique for molecular imaging., (© 2024. The Author(s).)

The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects. A multi-database search was used to identify original clinical and preclinical research articles examining RAGE expression in PCa. After screening and review, nine clinical and six preclinical articles were included. The associations of RAGE differentiating benign prostate hyperplasia (BPH) or normal prostate from PCa and between tumor grades were estimated using odds ratios (ORs) and associated 95% confidence intervals (CI). Pooled estimates were calculated using random-effect models due to study heterogeneity. The clinical meta-analysis found that RAGE expression was highly likely to be increased in PCa when compared to BPH or normal prostate (OR: 11.3; 95% CI: 4.4-29.1) and that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5; 95% CI: 1.8-3.4). In addition, meta-analysis estimates of preclinical studies performed by albatross plot generation found robustly positive associations among RAGE expression/activation and PCa growth and metastatic potential. This review demonstrates that RAGE expression is strongly tied to PCa progression and can serve as an effective diagnostic target to differentiate between healthy prostate, low-grade PCa, and high-grade PCa, with potential theragnostic applications.